pardoprunox and Dyskinesia--Drug-Induced

To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations.. Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale).. Pardoprunox significantly reduced OFF time versus placebo (-1.62 h/day versus -0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid.. Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.

Topics: Adult; Aged; Antiparkinson Agents; Benzoxazoles; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Pain Measurement; Parkinson Disease; Piperazines; Severity of Illness Index; Time Factors; Treatment Outcome

The objective of this study was to establish temporal stability characteristics for objective components of the Unified Dyskinesia Rating Scale (UDysRS). The UDysRS has strong internal consistency and a reliable factor structure, but the important issue of temporal stability has not been established.. Using intraclass correlation coefficient (ICC) analyses, we examined UDysRS temporal stability for the objective scale components (Part III and IV) over an 8-hour observation period. We assessed ICCs for the single centralized rater, the on-site raters, and the agreement between the single centralized rater and the on-site raters. Kappa statistic assessed agreement between the single centralized and on-site raters for clinical state (ON vs OFF).. For both the single centralized rater and the on-site raters, there was high temporal stability of the UDysRS Part III, Part IV, and Total Objective UDysRS in both ON and OFF states, with ICCs ranging from 0.822 (P < .0005) to 0.513 (P < .013). The agreement between the 2 rating techniques (centralized vs on-site) was significant for ON and OFF ratings of Part III, Part IV, and Total Objective UDysRS, ranging from 0.821 (P < .0005) to 0.703 (P < .0005).. The UDysRS is highly stable for ON and OFF. Our data suggest that a single UDysRS evaluation for ON and for OFF states is highly representative of that state regardless of time. Likewise, if appropriate protocols need to assess dyskinesia in a field or community setting, the UDysRS can be filmed without an on-site rater and rated centrally with retained validity.

Topics: Aged; Benzothiazoles; Benzoxazoles; Disability Evaluation; Dopamine Agonists; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Observer Variation; Parkinson Disease; Piperazines; Pramipexole; Reproducibility of Results; Videotape Recording